Block of Glutamate-Glutamine Cycle Between Astrocytes and Neurons Inhibits Epileptiform Activity in Hippocampus

1 Consiglio Nazionale delle Ricerche Institute of Neuroscience, Cellular and Molecular Pharmacology, Department of Medical Pharmacology, 20129 Milano; 2 Istituto Neurologico C. Besta, 20100 Milano; and 3 Università Degli Studi Dell'insubria, 21100 Varese, Italy Bacci, Alberto, Giulio Sancini, Claudia Verderio, Simona Armano, Elena Pravettoni, Riccardo Fesce, Silvana Franceschetti, and Michela Matteoli. Block of Glutamate-Glutamine Cycle Between Astrocytes and Neurons Inhibits Epileptiform Activity in Hippocampus. J. Neurophysiol. 88: 2302-2310, 2002. Recurrent epileptiform activity occurs spontaneously in cultured CNS neurons and in brain slices in which GABA inhibition has been blocked. We demonstrate here that pharmacological treatments resulting in either the block of glutamine production by astrocytes or the inhibition of glutamine uptake by neurons suppress or markedly decrease the frequency of spontaneous epileptiform discharges both in primary hippocampal cultures and in disinhibited hippocampal slices. These data point to an important role for the neuron-astrocyte metabolic interaction in sustaining episodes of intense rhythmic activity in the CNS, and thereby reveal a new potential target for antiepileptic treatments. * A. Bacci and G. Sancini contributed equally to this work.